Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
Tanenbaum Centre for Pharmacogenetics, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Can J Psychiatry. 2021 Dec;66(12):1019-1041. doi: 10.1177/0706743720971950. Epub 2020 Nov 23.
Individuals with intellectual disability (ID) and autism spectrum disorder (ASD) often receive psychotropic medications such as antipsychotics and antidepressants to treat aberrant behaviors and mood symptoms, frequently resulting in polypharmacy and drug-related adverse effects. Pharmacogenomic (PGx) studies with ASD and/or ID (ASD/ID) have been scarce despite the promise of optimizing treatment outcomes. We reviewed the literature on PGx studies with antipsychotics and antidepressants (e.g., treatment response and adverse effects) in ASD/ID.
We performed a systematic review using MEDLINE, Embase, and PsycINFO, including peer-reviewed original articles in English referring to PGx in the treatment of ASD/ID in any age groups (e.g., treatment response and adverse effects).
A total of 28 PGx studies using mostly candidate gene approaches were identified across age groups. Notably, only 3 studies included adults with ASD/ID while the other 25 studies focused specifically on children/adolescents with ASD/ID. Twelve studies primarily investigated treatment response, of which 5 and 6 studies included patients treated with antipsychotics and antidepressants, respectively. Most interesting results for response were reported for 2 sets of candidate gene studies, namely: (1) The (rs6280) polymorphism was examined in patients treated with risperidone in 3 studies, 2 of which reported an association with risperidone treatment response and (2) the 5-HTTLPR polymorphism and treatment response to antidepressants which was investigated in 4 studies, 3 of which reported significant associations. In regard to side effects, 9 of 15 studies focused on hyperprolactinemia in patients treated with risperidone. Among them, 7 and 5 studies examined the impact of and polymorphisms, respectively, yielding mostly negative study findings.
There is limited data available on PGx in individuals with ASD/ID and in particular in adults. Given the potential for PGx testing in improving treatment outcomes, additional PGx studies for psychotropic treatment in ASD/ID across age groups are warranted.
智障（ID）和自闭症谱系障碍（ASD）患者经常接受抗精神病药和抗抑郁药等精神药物治疗，以治疗异常行为和情绪症状，这常常导致多种药物治疗和与药物相关的不良反应。尽管有优化治疗效果的前景，但针对 ASD 和/或 ID（ASD/ID）的药物基因组学（PGx）研究却很少。我们综述了 ASD/ID 患者使用抗精神病药和抗抑郁药（如治疗反应和不良反应）的 PGx 研究文献。
我们使用 MEDLINE、Embase 和 PsycINFO 进行了系统综述，包括针对任何年龄段 ASD/ID 患者的 PGx 治疗的同行评审原始文章（如治疗反应和不良反应）。
共确定了 28 项使用候选基因方法的 PGx 研究，涵盖了不同年龄段。值得注意的是，只有 3 项研究纳入了 ASD/ID 成年患者，而其他 25 项研究则专门针对 ASD/ID 儿童和青少年患者。12 项研究主要研究了治疗反应，其中 5 项和 6 项研究分别包括接受抗精神病药和抗抑郁药治疗的患者。对于反应，有两组候选基因研究报告了最有趣的结果，分别是：（1）在 3 项研究中，检查了（rs6280）多态性与利培酮治疗反应的关系，其中 2 项研究报告了与利培酮治疗反应的相关性；（2）5-HTTLPR 多态性与抗抑郁药治疗反应的关系，在 4 项研究中进行了研究，其中 3 项研究报告了显著的相关性。关于副作用，15 项研究中有 9 项关注利培酮治疗患者的高催乳素血症。其中，7 项和 5 项研究分别检查了和 多态性的影响，主要得出了否定的研究结果。
针对 ASD/ID 患者，特别是成年患者的 PGx 数据有限。鉴于 PGx 检测在改善治疗效果方面的潜力，需要在不同年龄段的 ASD/ID 患者中开展更多的精神药物治疗 PGx 研究。
